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V. T. Ciavatta, M. K. Kim, Y. Cao, M. H. Aung, J. Mocko, M. T. Pardue; Effect of Subretinal Electrical Stimulation Dose on Growth Factor Expression in RCS Rat Retinae. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4513.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies showed preservation of photoreceptors and dark-adapted ERG responses after 4 - 6 weeks of subretinal electrical stimulation (SES) from a subretinally-implanted microphotodiode array (MPA) (Pardue et al., IOVS 2005) and selective induction of Fgf2 after 1 and 4 weeks of SES (Ciavatta et al., IOVS 2009) in RCS rats. The present study examined the effects of increasing SES current and frequency of administration on retinal growth factor expression in RCS rats at 1 and 4 weeks after implantation.
At postnatal day 21, RCS rats were monocularly implanted with a functional MPA and followed for 1 or 4 weeks. SES dose groups consisted of implanted-only (1 wk, n=14; 4 wk, n=4), low dose (450 µA/cm2) (n=4-6/group), and high dose (1350 µA/cm2) (n=4-6/group). Doses were administered 1, 3, or 5 times per week for 15 minutes per treatment with an 873 nm infrared light (IR). For each treatment group, rats receiving no MPA controlled for effects of IR. ERGs were measured weekly beginning seven days after surgery. Real-time RT-PCR was used to measure relative expression of Fgf2 in retina samples collected 2 days after the final ERG.
One week after surgery, Fgf2 expression in treated versus opposite eyes was 4.67 +/-0.72, 6.04 +/-1.24, 7.49 +/-2.15, and 3.09 +/-0.33 (mean +/-sem) in the implanted-only, once per week, 3 times per week, and 5 times per week low dose groups, respectively. Fgf2 expression was greatest in the 3 times per week treatment group (P = 0.032, ANOVA). However, after one week of high dose SES, there were no differences in Fgf2 expression between implanted-only and dosed groups. Similarly, after 4 weeks of either high or low dose SES, there were no differences in Fgf2 expression between implanted-only and dosed groups (P = 0.102, ANOVA).
We previously observed that SES of RCS rats produces measurable neuroprotection (by ERG and histology) and induction of Fgf2. Further, the neuroprotective response depended on SES current dose (Kim et al, 2007 E-ARVO abstract 656). This study was undertaken to further investigate a dose response and role of Fgf2 in the neuroprotective mechanism. While Fgf2 expression did increase with increased frequency of SES, it was not significantly different than implanted-only retina. Thus, the increased functional protection with higher SES current dose may be due to other survival factors in the retina.
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